TANGO1 inhibitors reduce collagen secretion and limit tissue scarring - Université Paris Cité Accéder directement au contenu
Article Dans Une Revue Nature Communications Année : 2024

TANGO1 inhibitors reduce collagen secretion and limit tissue scarring

Ishier Raote
Ann-Helen Rosendahl
Hanna-Maria Häkkinen
  • Fonction : Auteur
Carina Vibe
  • Fonction : Auteur
Ismail Küçükaylak
  • Fonction : Auteur
Mugdha Sawant
  • Fonction : Auteur
Lena Keufgens
  • Fonction : Auteur
Pia Frommelt
  • Fonction : Auteur
Kai Halwas
  • Fonction : Auteur
Katrina Broadbent
  • Fonction : Auteur
Marina Cunquero
Gustavo Castro
  • Fonction : Auteur
Julian Nüchel
Anna Bornikoel
Binita Dam
  • Fonction : Auteur
Ravindra K Zirmire
  • Fonction : Auteur
Ravi Kiran
Carlo Carolis
Jordi Andilla
Pablo Loza-Alvarez
Verena Ruprecht
Colin Jamora
Felix Campelo
Marcus Krüger
Matthias Hammerschmidt
Beate Eckes
Ines Neundorf
Thomas Krieg
  • Fonction : Auteur
Vivek Malhotra

Résumé

Abstract Uncontrolled secretion of ECM proteins, such as collagen, can lead to excessive scarring and fibrosis and compromise tissue function. Despite the widespread occurrence of fibrotic diseases and scarring, effective therapies are lacking. A promising approach would be to limit the amount of collagen released from hyperactive fibroblasts. We have designed membrane permeant peptide inhibitors that specifically target the primary interface between TANGO1 and cTAGE5, an interaction that is required for collagen export from endoplasmic reticulum exit sites (ERES). Application of the peptide inhibitors leads to reduced TANGO1 and cTAGE5 protein levels and a corresponding inhibition in the secretion of several ECM components, including collagens. Peptide inhibitor treatment in zebrafish results in altered tissue architecture and reduced granulation tissue formation during cutaneous wound healing. The inhibitors reduce secretion of several ECM proteins, including collagens, fibrillin and fibronectin in human dermal fibroblasts and in cells obtained from patients with a generalized fibrotic disease (scleroderma). Taken together, targeted interference of the TANGO1-cTAGE5 binding interface could enable therapeutic modulation of ERES function in ECM hypersecretion, during wound healing and fibrotic processes.
Fichier principal
Vignette du fichier
s41467-024-47004-1.pdf (3.21 Mo) Télécharger le fichier
Origine Fichiers éditeurs autorisés sur une archive ouverte
Licence

Dates et versions

hal-04590865 , version 1 (28-05-2024)

Licence

Identifiants

Citer

Ishier Raote, Ann-Helen Rosendahl, Hanna-Maria Häkkinen, Carina Vibe, Ismail Küçükaylak, et al.. TANGO1 inhibitors reduce collagen secretion and limit tissue scarring. Nature Communications, 2024, 15 (1), pp.3302. ⟨10.1038/s41467-024-47004-1⟩. ⟨hal-04590865⟩
2 Consultations
1 Téléchargements

Altmetric

Partager

Gmail Mastodon Facebook X LinkedIn More